Scientific Core - Pharmaceutics and Medicinal Chemistry

科学支持核心：药剂学和药物化学科学支持核心 关键人员： 帕特里克J. Sinko博士，创新药物递送团队核心联合负责人、联合负责人 内德·D Heindel博士，核心联席负责人、联席负责人、规模扩大和生产支持团队 Christophe Guillon博士，领导者，化合物库和规模扩大和制造支持团队 劳里约瑟夫博士，临床前制剂团队负责人 Dipti Kakkar Thukral博士，创新药物输送团队 核心摘要/摘要 药剂学和药物化学科学支持核心与中心研究者密切合作 在研究和开发项目以及药理学和药物开发核心中， 发现并优化可使用的先导药物和预期制剂/药物递送系统（DDS） 治疗发泡剂中毒，并协助其发展成药物产品，以获得FDA的批准。在 为了快速将研究项目的机械发现转化为临床，我们的中心 确定了FDA批准用于其他治疗适应症的药物产品，并建议将其用于 治疗水疱性中毒，一个新的适应症。我们目前正在处理IND申请， 中心研究者完成IND使能研究，以支持Pre-IND FDA会议。临床前 制剂焦点团队与药理学和药物开发核心以及 研究项目团队生产稳定的临床前制剂，用于初步疗效和毒理学 考核创新药物递送焦点小组正在开发新型DDS，以克服 生物制药障碍（例如，蛋白质不稳定性、渗透性差或清除率高）或生理化学 但也存在水溶性差或不稳定等局限性。为稳定性提供分析化学支持 对配制的活性药物成分（API）、代谢物鉴定和药代动力学的研究， 毒代动力学和药效学研究。化合物库支持团队正在优化API 具有先前确定的先导化合物的化合物类别和新的化合物类别正在开发中。规模- up和制造支持团队确保合成工艺的可扩展性，工艺改进， 优化多步途径，临床级材料的可用性和所述 合同生产组织的纯度证书。为了促进对策API充分 在IND前状态下，药物化学团队与研究项目密切合作， 确定最有效的治疗化合物和备用候选物。科学支持核心 然后制定临床前方案规范，包括所需剂量、给药间隔， 药代动力学使用这些规范，制药团队改进了DD平台技术 具体候选药物和交付规格。简而言之，开发过程高度 协作和迭代。

Scientific Support Core: Pharmaceutics and Medicinal Chemistry Scientific Support Core Key Personnel: Patrick J. Sinko, Ph.D., Core Co-Lead, Co-Leader, Innovative Drug Delivery Team Ned D. Heindel, Ph.D., Core Co-Lead, Co-Leader, Scale-up and Manufacturing Support Team Christophe Guillon, Ph.D., Leader, Compound Library & Scale-up and Manufacturing Support Teams Laurie Joseph, Ph.D., Leader, Pre-clinical Formulations Team Dipti Kakkar Thukral, Ph.D., Innovative Drug Delivery Team Core Summary/Abstract The Pharmaceutics and Medicinal Chemistry Scientific Support Core works closely with Center investigators within the Research and Development Projects and the Pharmacology and Drug Development Core to discover and optimize lead agents and prospective formulations/drug delivery systems (DDS) that can be used to treat vesicant poisoning, and to assist in their development into drug products for approval by the FDA. In order to rapidly translate mechanistic discoveries from the research projects to the clinic, our Center has identified drug products approved by the FDA for other therapeutic indications, and proposed their use for treating vesicant toxicity, a new indication. We currently have IND applications in process and are working with Center investigators to complete IND-enabling studies in support of Pre-IND FDA meetings. The Pre-clinical Formulations Focus Team works closely with the Pharmacology and Drug Development core and the Research project teams to produce stable preclinical formulations for initial efficacy and toxicological assessment. The Innovative Drug Delivery Focus Team is developing novel DDS in order to overcome biopharmaceutical barriers (e.g., protein instability, poor permeability, or high clearance) or physiochemical limitations such as poor aqueous solubility or instability. Analytical chemistry support is provided for stability studies on formulated Active Pharmaceutical Ingredients (APIs), metabolite identification, and pharmacokinetic, toxicokinetic and pharmacodynamics studies. The Compound Library Support Team is optimizing API compound classes with previously identified leads and new compound classes are in development. The Scale- up and Manufacturing Support Team assures the scalability of synthetic processes, process improvements, optimization of multi-step pathways, and availability of clinical grade material and confirmation of the stated certificate of purity by Contract Manufacturing organizations. In order to promote a countermeasure API to full pre-IND status, the Medicinal Chemistry team works closely and iteratively with the research projects to determine the most efficacious therapeutic compounds and backup candidates. This Scientific Support core then develops the preclinical regimen specifications including dose required, dosing interval, and pharmacokinetics. Using these specifications, the Pharmaceutics team refines the DD platform technologies for the specific drug candidate and delivery specifications. In short, the development process is highly collaborative and iterative.